Hematopoietic stem and progenitor cells (HSPC) self-renew and differentiate to form all blood cells throughout animal life. The hematopoietic system is composed of many different cell types at various stages of maturity. HSCs give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells).
As stem cells, they are defined by their ability to form multiple cell types (multipotency) and their ability to self-renew. It is known that a small number of HSCs can expand to generate a very large number of progeny HSCs. This phenomenon is used in bone marrow transplant when a small number of HSCs reconstitute the hematopoietic system. The ability to self-renew and differentiate to form all blood cells provides a constant supply of blood cells throughout animal life. The supply is needed for replacing old, worn out or dead blood cells in the body.
The intricate balance between the two characteristic self-renewal and differentiation stem cell states is required for maintaining hematopoietic homeostasis and for responding to tissue injury. Stem cell population size is tightly regulated and thought to be dictated by rates of proliferation, relative frequency of differentiative versus self-renewal outcomes and apoptosis. Disruption of any of these processes could lead to stem cell exhaustion or increased risk of leukemogenesis (1-5). However, the molecular events specifying stem cell population size are still poorly understood. Identifying the genes and pathways that regulate self-renewal and differentiation in HSCs can provide ways to regulate stem cell fate and the development of conditions that would enable amplification of transplantable HSCs.